Targeted lymph-node immunization with whole inactivated simian immunodeficiency virus (SIV) or envelope and core subunit antigen vaccines does not reliably protect rhesus macaques from vaginal challenge with SIVmac251.
OBJECTIVE
Sexual transmission of HIV is the most common route of HIV transmission throughout the world. To prevent sexually transmitted HIV infection, a vaccine is urgently needed. A previous report demonstrated the targeted immunization of the iliac lymph nodes with simian immunodeficiency virus (SIV) subunits protects rhesus macaques from rectal challenge with SIV. We sought to determine whether this immunization strategy could protect rhesus macaques from vaginal challenge with SIV.


METHODS
Macaques were immunized with either whole-killed SIV or envelope and core subunit antigen vaccines. Using three independent groups, with three macaques in each group, macaques were immunized by the targeted iliac lymph-node (TILN) route, injecting the vaccine close to the iliac lymph nodes that drain the genital tract.


RESULTS
The TILN immunization procedure induced high-titer SIV-specific immunoglobulin (Ig) G antibodies in serum in all animals and anti-SIV IgG and IgA antibodies in the cervicovaginal secretions of most animals. After a series of three or four TILN immunizations, the animals were intravaginally challenged with SIVmac251. All animals became virus isolation-positive, except one animal immunized with SIV p27 and gp120. This animal was virus isolation-negative but SIV DNA proviral sequences were detected in peripheral blood mononuclear cells.


CONCLUSIONS
In this series of studies, reliable protection from vaginal transmission of SIV was not achieved by the TILN immunization procedure.
Lü
X
X
California Regional Primate Research Center, School of Veterinary Medicine, University of California Davis, USA.
Kiyono
H
H
Lu
D
D
Kawabata
S
S
Torten
J
J
Srinivasan
S
S
Dailey
P J
PJ
McGhee
J R
JR
Lehner
T
T
Miller
C J
CJ
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000097:blood / Q000276:immunology; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000276:immunology; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics / Q000276:immunology; D018562:Disease Transmission, Infectious; D005260:Female; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D007085:Ilium; D007070:Immunoglobulin A / Q000032:analysis / Q000276:immunology; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D007075:Immunoglobulin M / Q000032:analysis / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000821:virology; D008198:Lymph Nodes / Q000276:immunology*; D008251:Macaca; D008562:Membrane Glycoproteins; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D018449:SAIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000635:transmission; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014621:Vagina / Q000276:immunology / Q000821:virology; D014759:Viral Envelope Proteins
D000914:Antibodies, Viral; D004279:DNA, Viral; C066594:Gag protein p27, Simian immunodeficiency virus; D015683:Gene Products, gag; D015699:HIV Envelope Protein gp120; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D012367:RNA, Viral; D018449:SAIDS Vaccines; D015164:Vaccines, Inactivated; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus